The liver, with over 500 functions, is one the most significant and versatile organ of the human body. It weighs around 1.5kg and it is divided into four lobes; left, right, quadrate and caudate. It is wrapped in a fibrous capsule which is covered by the visceral peritoneum.
30% of the bloody supply of the heart reaches the liver at a region called the Hilus every minute, of which two thirds is through the portal vein and a third through the hepatic artery, it then leaves the liver through the hepatic vein. Blood pressure is low, usually at 10mm Hg or less.
The cells of the liver are known as Hepatocytes. Hepatocytes serve many roles in the functions of the liver of which include: Metabolic regulation; it plays a key role in the metabolism of carbohydrates, fats and proteins, Haematological regulation; it is the primary organ that regulates the composition of blood, and Bile synthesis.
[2] During carbohydrate metabolism, most of the glucose that is derived from the breakdown of carbohydrates is stored as glycogen in the liver cells (Glycogenesis) until it is needed, which is when the liver will convert the glycogen back into glucose to be used for respiration (Glycogenolysis). Examples of such situations are when there is a short supply of glucose in the body during the times between meals or when fasting.
When the body is starved from carbohydrates, the liver can produce glucose by a process called Gluconeogenesis by converting amino acids from dietary and body proteins, lactate or glycerol into glucose. This prevents the individual from having hypoglycaemia (low blood glucose levels), so by this it can also be said that the liver has an integral part of maintaining blood glucose levels.
The liver serves a major role in fat metabolism by producing the lipoproteins that are needed to transport fat, cholesterol and triglycerides in the blood throughout the body.
Protein metabolism takes place in the liver as it goes through amino acid conversion, most of the amino acids are synthesised into proteins that are needed for the body, especially albumin which is the main plasma protein. Amino acid metabolism however produces a waste product, Urea, which is transported to the kidneys via blood and excreted through urine.
Haematological regulation is the way in which the liver processes the blood by regulating the amount of chemicals it holds and breaking down the nutrients within it so it is easy to use. It also detoxifies toxic substances such as drugs or alcohol that come via blood and breaks it down before being released back into the blood into amounts that can be handled by the body.
In addition to its metabolic functions, it is also responsible for the production of bile. Bile is a yellow alkaline fluid that is produced by the hepatocytes made up of mainly water (85%) and bile salts (10%). Bile salts acts as a fat emulsifier so it is needed for the normal digestion and absorption of ingested fats. Bile also serves as a route in which substances such as drugs and wastes produced from metabolism that aren’t removed by the kidneys, such as bilirubin, is removed from the body through the faeces. Hepatocytes secrete bile into tubes known as Bile Canaliculi, which jointo form Bile Ductules. Bile ductules then transport bile to the nearest portal area. The right and left hepatic ducts collects the bile from the ductules at the portal areas and merge to form the Common Hepatic Duct. This leaves the liver to go to the gall bladder through the Cystic Duct which joins onto the Common Bile Duct which transports bile to the duodenum through the Duodenal Ampulla and then goes into the small intestine ready to act upon the absorption of fats.
[2] These are only a few functions of the liver, all of which if do not function properly can lead to many liver diseases. Diseases can generally be classified into two types; Hepatocellular, which results in damage to the hepatocytes and Cholestatic which restricts bile flow due to blockage in ducts.
Most patients suffering from a liver disease develop jaundice resulting from high levels of the bilirubin in the blood stream (hyperbilirubinemia). Jaundice makes whites of the eyes yellow and then gradually the skin start becoming yellow. Bilirubin is produced from dead red blood cells; at the end of their life span, the haemoglobin found within them is released and split into haem and globin. Iron from haem is recycled for the production of more haemoglobin and any remains of the haem molecule are converted to bilirubin. It is excreted in the faeces and some in the urine. It is elevated in most liver diseases as they cause some sort of damage to hepatocytes which means bilirubin cannot conjugate with glucuronic acid in order to be excreted, so it stays in the bloodstream where its levels continuously increase.
One of the common diseases to occur in the liver is Hepatitis. It results in inflammation of the liver cells. Viral Hepatitis can be caused by Hepatitis A, B, C, D, E, yellow fever or Herpes Simplex. Patients usually start off small with flu like symptoms.
Non viral hepatitis can be due to auto immune reasons, drugs, toxins found in mushrooms and alcohol. [3] ‘As alcohol consumption is very high in the western world, alcohol hepatitis is a common problem. Symptoms include enlargement of the liver, development of fluid in the abdomen (ascites), increased blood pressure in the portal vein and later development of jaundice. If alcoholic hepatitis is diagnosed it is important to stop consuming alcohol at once otherwise it could lead to more serious damage such as cirrhosis or even liver failure.’
[2] Cirrhosis is an irreversible liver disease. Patients with cirrhosis develop ascites, jaundice and the formation of fibrous tissue where liver cells should be, the liver cells are destroyed in response to toxic chemicals, a viral hepatitis, or most commonly, high alcohol consumption. These are examples of Hepatocellular liver diseases.
An example of a Cholestatic liver disease would be Cholestasis. Cholestasis is a state when there is a blockage in the bile ducts so bile cannot be released. Again, jaundice develops when a patient suffers from cholestasis as bilirubin is also unable to reach the small intestine to be excreted. Other symptoms include pale faeces and dark urine.
There are a number of tests available that determines liver diseases. These include bilirubin, ALP, ALT and the GGT tests. A slightly abnormal bilirubin concentration indicates it may be haemolytic anaemia (abnormal rate of red blood cell destruction). A higher concentration is due to diseases which have damaged the hepatocytes therefore bilirubin cannot conjugate or be excreted properly. These diseases are acute hepatitis and alcoholic hepatitis. A very high concentration indicates cholestasis as it means bile flow is completely blocked (most commonly by gallstones) and so bilirubin cannot be excreted. Bilirubin can be measured by taking a blood test; conjugated, unconjugated or total bilirubin. Conjugated bilirubin is bound to glucuronic acid and so is called direct bilirubin. Unconjugated bilirubin is measured by subtracting the direct bilirubin from the total bilirubin, so is called indirect bilirubin. Total Bilirubin is the term used when both are measured.
GGT, ALP and ALT are all enzymes that are present in the liver cells. Hepatocyte death (necrosis) leads to large amounts of these enzymes to be released into the blood stream which if measured will serve as an indicator of liver disease. These enzymes can be measured by taking around 5 ml of venous blood. Abnormal ALT (alanine transferase) results are found in diseases that have come about as a result of necrosis. In acute hepatitis, ALT rises before jaundice develops and then usually goes back to normal within 8 weeks. A continuous raised level of ALT means that it chronic liver disease such as chronic hepatitis or cirrhosis.
High GGT (gamma glutamyl transferase) levels are found in all liver and biliary tract diseases. GGT doesn’t determine an actual disease but it is used to predict who may be at risk of liver disease due to alcohol as it is the only enzyme that is produced due to alcohol, so high continuous levels would mean alcoholic hepatitis or cirrhosis.
Moderately results of ALP (alkaline phosphatise) indicate acute hepatitis but extremely high results show cholestasis may have developed. However, ALP is also present in the cells of the bone, so only measuring it by itself would not be an accurate indication of liver disease. It is usually measured alongside GGT; if both levels are high then it confirms that the problem is definitely within the liver.
These are a few diseases and tests that are commonly used today to identify one of the biggest causes of death in the UK today.
References:[1] Martini, F., H., 2004, Fundamentals of Anatomy and Physiology, 6th edition, San Francisco: Benjamin Cummings, ISBN: 0-13-120346-0.
[2] Higgins, C., 2000, Understanding Laboratory Investigations, Oxford: Blackwell Science Ltd, ISBN: 0-632-04245-1
[3] Mayo Clinic Staff, 2010, Alcoholic Hepatitis, Mayo Clinic, DS00785
